CN117279561A

CN117279561A - Device for monitoring peritoneal dialysis infection

Info

Publication number: CN117279561A
Application number: CN202280028779.0A
Authority: CN
Inventors: 苏雷什·贝鲁尔·本卡塔拉亚; 曼达尔·马诺哈尔·戈里; 林智诚; 王越; 彼得·海伍德; 里卡多·阿吉拉尔·格拉赫达; 亚历山德罗·多纳迪奥
Original assignee: Awak Technologies Pte Ltd
Current assignee: Awak Technologies Pte Ltd
Priority date: 2021-04-15
Filing date: 2022-04-14
Publication date: 2023-12-22
Also published as: TW202245851A; AU2022259371A1; CA3215227A1; EP4322832A1; WO2022220753A1; KR20240014044A; JP2024517605A

Abstract

The present disclosure relates to a device (200) for monitoring an infection of a peritoneal dialysis patient (102). The device (200) comprises: a housing module (202) removably connected to a fluid element (204) configured to receive spent dialysate (130) from a patient (102); a set of lighting elements (206) disposed on the chamber module (202) and configured to emit light into the fluid element (204); a set of optical sensors (208) disposed on the housing module (202) and configured to measure optical properties of light interacting with the spent dialysate (130) in the fluid element (204); and a control module configured to measure a turbidity of the spent dialysate (130) based on the optical property, wherein the dialysate turbidity indicates the patient (102) is infected if the dialysate turbidity meets a set of predefined conditions with a historical dialysate turbidity of the patient (102).

Description

Device for monitoring peritoneal dialysis infection

Cross Reference to Related Applications

The present invention claims the benefit of singapore patent application No. 10202083858V, 4-15-2021, which is incorporated herein by reference in its entirety.

Technical Field

The present invention relates generally to devices for monitoring peritoneal dialysis infections, and more particularly, to various embodiments of devices for monitoring infections such as peritonitis in peritoneal dialysis patients.

Background

Millions of people worldwide suffer from kidney-related problems such as chronic kidney disease (Chronic Kidney Disease, CKD) and End-stage kidney disease (End-Stage Renal Disease, ESRD), and they require dialysis or transplantation to sustain life. There are two modes of dialysis-hemodialysis and peritoneal dialysis. In hemodialysis, blood is pumped from a patient to a dialysis machine, which filters the blood and returns the filtered blood to the body. In peritoneal dialysis, the peritoneum in the abdomen of a patient acts as a natural filtration membrane. Although dialysis provides a survival modality for renal failure, it is still associated with significant changes in quality of life. Performing dialysis at home, rather than in a clinical setting, can help to improve the quality of life of the patient, as it can normalize daily life, and the patient can schedule dialysis according to their activity plan. However, home dialysis presents challenges. The patient or patient's caregivers need to learn how to perform home dialysis themselves, especially peritoneal dialysis, and the procedure can be quite cumbersome.

Fig. 1 illustrates an exemplary peritoneal dialysis apparatus 100 that is used by a patient 102 at home. The patient 102 has an adapter 104 comprising a catheter that is inserted into the abdomen of the patient. At the beginning of peritoneal dialysis, the patient 102 connects the adapter 104 to a common line or tubing or patient line 106 leading to a tubing connector 108. The adapter 104 has a valve 105 to open and close the conduit, which should normally be closed to prevent infection. A fresh bag 110 containing fresh dialysate or solution is connected to the line connector 108 via a supply line or fill line 112. The fill line 112 has a valve 114 to open and close the fill line 112 at appropriate stages during peritoneal dialysis. A drain bag 116 is connected to the tubing connector 108 via a drain line or drain line 118. The drain line 118 has a valve 120 to open and close the drain line 118 at appropriate stages during peritoneal dialysis.

During peritoneal dialysis, fresh dialysate flows from the fresh bag 110 into the abdomen, where the peritoneum allows waste compounds and excess fluid to pass from the blood into the fresh dialysate. Fresh dialysate contains sugar, such as glucose/dextrose, as the primary osmotic agent to achieve fluid removal or filtration across the peritoneum into the abdominal cavity. The spent dialysate is then drained from the body as spent dialysate, which contains spent compounds and excess fluid. The spent dialysate is collected in a drainage bag 116 and discarded. The apparatus 100 may be configured to exchange fluid by gravity. Alternatively, the apparatus 100 may include a machine or pump 122 for fluid exchange, such as when the patient 102 is sleeping.

The apparatus 100 allows the patient 102 to receive peritoneal dialysis treatment at home or on the fly without significantly compromising his/her quality of life. However, the patient 102 should be careful to avoid contamination when handling the device 100. For example, the patient 102 may not be able to properly connect the adapter 104 to the common line 106 due to, for example, under training, and risk of hand contact contamination on the adapter 104 and/or the tip of the common line 106. This contamination may cause infection of patient 102, such as peritonitis.

Peritonitis can be detected by visual observation of the turbidity or turbidity of the spent dialysate in the drainage bag 116 and observation of any symptoms associated with abdominal pain. However, observing the cloudiness of the spent dialysate is very subjective and small changes in cloudiness may not be readily noticeable to the naked eye. For this work, different patients 102 may also have different visual acuity. Early stage peritonitis can cause an imperceptible slight turbidity to patient 102, resulting in delayed diagnosis and treatment. Thus, there is an inconsistency in the quality of the examination of the patient 102, with some cases of peritonitis missing and some cases of non-peritonitis being incorrectly identified as positive. In addition, some peritonitis patients 102 may be asymptomatic during the early stages and symptoms such as mild abdominal pain may be mistakenly attributed to other factors, resulting in delayed diagnosis and treatment. It may take only a few days for the turbidity to become more pronounced and/or for the symptoms to become more severe. But also means that peritonitis progresses to a more advanced stage, making treatment more difficult, resulting in increased mortality.

Accordingly, to address or mitigate at least one of the above-identified problems and/or disadvantages, there is a need to provide improved devices for monitoring peritoneal dialysis infections.

Disclosure of Invention

According to a first aspect of the present invention, there is provided a device for monitoring infection in a patient for peritoneal dialysis. The device comprises:

a housing module removably connected to a fluid element configured to receive spent dialysate from the patient;

a set of illumination elements disposed on the chamber module and configured to emit light into the fluid element;

a set of optical sensors disposed on the chamber module and configured to measure optical properties of light that has interacted with spent dialysate in the fluidic element; and

a control module configured to measure the turbidity of the spent dialysate based on the optical property,

wherein the dialysate turbidity indicates the patient is infected if the dialysate turbidity and the patient's historical dialysate turbidity meet a set of predefined conditions.

According to a second aspect of the present invention, there is provided a device for monitoring infection in a patient for peritoneal dialysis. The device comprises:

a color sensor configured to measure color information of a reagent test element disposed in the fluid element, the reagent test element having reacted with the spent dialysate in the fluid element; and

A control module configured to monitor for infection based on the color information, the color information representing an enzymatic activity in the spent dialysate, indicative of the patient's infection.

According to a third aspect of the present invention, there is provided a device for monitoring infection in a peritoneal dialysis patient. The device comprises:

a housing module removably connected to a fluid element configured to receive spent dialysate from a patient;

a set of optical sensors disposed on the chamber module and configured to:

measuring an optical property of light that has interacted with spent dialysate in the fluid element; and

measuring color information of a reagent test element disposed in the fluid element, the reagent test element having reacted with the spent dialysate in the fluid element; and

a control module configured to:

measuring a turbidity of the spent dialysate based on the optical property, the dialysate turbidity being indicative of the patient's infection if the dialysate turbidity and the patient's historical dialysate turbidity meet a set of predefined conditions; and

infection is monitored based on the color information, which represents enzyme activity in the spent dialysate, which is indicative of patient infection.

According to a fourth aspect of the present invention, a computerized method of monitoring infection in a patient for peritoneal dialysis is provided. The method comprises the following steps:

measuring color information of a reagent test element that has reacted with waste dialysate from the patient;

extracting RGB color data from the color information; and

infection is monitored based on the RGB color data, which represents enzyme activity in the spent dialysate, which is indicative of the patient's infection.

Accordingly, disclosed herein are devices of the present invention for monitoring peritoneal dialysis infection. Various features, aspects, and advantages of the present invention will become more apparent from the following detailed description of exemplary embodiments of the invention, given by way of non-limiting example only, accompanying drawings.

Drawings

Fig. 1 is a schematic diagram of a peritoneal dialysis apparatus.

Fig. 2A and 2B are schematic diagrams of an apparatus for monitoring infection based on turbidity of spent dialysate.

Fig. 3A and 3B are schematic diagrams of the apparatus of fig. 2A and 2B used with a peritoneal dialysis device.

Fig. 4A to 4C are standard curve diagrams of the apparatus of fig. 2A and 2B.

Fig. 5 is a schematic diagram of an apparatus for monitoring infection based on color information of a reagent test.

Fig. 6A and 6B are schematic views of the apparatus of fig. 5 in use with a peritoneal dialysis device.

FIG. 7 is a schematic representation of enzyme activity in spent dialysate.

Fig. 8A and 8B are schematic illustrations of the apparatus of fig. 2A, 2B and 5 used with a peritoneal dialysis device.

Fig. 9 is a schematic diagram of an apparatus for monitoring infection based on turbidity of spent dialysate and color information of a reagent test.

Fig. 10A and 10B are schematic illustrations of the apparatus of fig. 9 used with a peritoneal dialysis device.

Fig. 11A and 11B are other schematic diagrams of an apparatus for monitoring infection based on turbidity of waste dialysate and color information of reagent tests.

Detailed Description

For simplicity and clarity, the description of specific embodiments of the invention is directed to a device for monitoring peritoneal dialysis infection according to the accompanying drawings. While various aspects of the invention will be described in conjunction with the embodiments provided herein, it will be understood that they are not intended to limit the invention to these embodiments. On the contrary, the invention is intended to cover alternatives, modifications and equivalents of the specific embodiments described herein, which are included within the scope of the invention as defined by the claims. Furthermore, in the following detailed description, specific details are set forth in order to provide a thorough understanding of the present invention. However, it will be understood by those skilled in the art (i.e., by those skilled in the art) that the present invention may be practiced without the specific details and/or with a plurality of details that stem from a combination of aspects of the specific embodiments. In various instances, well-known systems, methods, procedures, and components have not been described in detail so as not to unnecessarily obscure aspects of the embodiments of the present invention.

The description of a given component or the consideration or use of a particular component symbol in a particular figure or with reference to corresponding descriptive material may include the same, equivalent or similar components or component numbers as indicated in another figure or in descriptive material associated therewith.

References to "one embodiment/example," "another embodiment/example," "some embodiments/examples," "some other embodiments/examples," etc., indicate that the embodiment(s) described may include a particular feature, structure, characteristic, property, component, or limitation, but every embodiment/example does not necessarily include the particular feature, structure, characteristic, property, component, or limitation. Furthermore, repeated use of the phrase "in one embodiment/example" or "in another embodiment/example" does not necessarily refer to the same embodiment/example.

The terms "comprising," "including," "having," and the like, do not exclude the presence of other elements/features than those listed in a particular embodiment. The mention of particular features/components/steps in mutually different embodiments does not indicate that such a combination of features/components/steps cannot be used in a particular embodiment.

The terms "a" and "an", as used herein, are defined as one or more. The use of "/" in the drawings or related text should be understood to mean "and/or" unless otherwise indicated. The term "group" is defined as a non-empty finite organization of components that mathematically presents at least one cardinality according to known mathematical definitions (e.g., a group as defined herein may correspond to a unit, a single state, or a single component group, or a group of multiple components). The terms "first," "second," and the like are used merely as labels or identifiers and are not intended to impose numerical requirements on their relative terms.

In some representative and exemplary embodiments of the present invention, referring to fig. 2A and 2B, there is an apparatus 200 for use with a peritoneal dialysis device 100 for monitoring infection of a peritoneal dialysis patient 102. The apparatus 200 includes a housing module 202 that is detachably connected to a fluid element 204 configured to receive the spent dialysate 130 from the patient 102. The fluid element 204 may have various cross-sectional shapes, such as a cylindrical shape. The apparatus 200 includes a set of illumination elements 206 disposed on the chamber module 202 and configured to emit light into the fluid element 204. The apparatus 200 includes a set of optical sensors 208 disposed on the housing module 202 and configured to measure optical properties of light interacting with the spent dialysate 130 in the fluid element 204. The apparatus 200 includes a control module configured to measure the turbidity of the spent dialysate 130 based on optical properties, wherein the dialysate turbidity indicates the patient 102 is infected, such as peritonitis, if the dialysate turbidity of the patient 102 and the historical dialysate turbidity meet a set of predefined conditions.

In some embodiments, the lighting element 206 includes one or more Light Emitting Diodes (LEDs). For example, the LEDs may include white LEDs. Alternatively, the LED may emit light of a specific wavelength or a narrow wavelength range, such as 860nm infrared light.

In some embodiments, the optical sensor 208 includes a scattered light sensor 208a that measures light that has been scattered by the spent dialysate 130. In some embodiments, the optical sensor 208 includes a transmission light sensor 208b that measures light that has been transmitted through the spent dialysate 130. Notably, the transmissive light sensor 208b and the illumination element 206 are disposed on the chamber module 202 such that the fluid element 204 is therebetween. In some embodiments, as shown in fig. 2A, the optical sensor 208 includes a scattered light sensor 208a and a transmitted light sensor 208b. For example, the scattered light sensor 208a and the transmitted light sensor 208b are located in different areas of the chamber module 202 for measuring scattered light and transmitted light, respectively. The type of optical sensor 208 may be selected based on the type of lighting element 206. For example, the scattered light sensor 208a and the transmitted light sensor 208b may use the same type of optical sensor or photodetector. The optical properties may include a relationship between scattered light and transmitted light.

When patient 102 suffers from peritonitis, bacteria, mycobacteria, fungi, and parasites in the peritoneum can initiate the production of leukocytes or leukocytes, which are markers of inflammation of the infection. The size of the leukocytes is typically in the range of 12 to 14 microns and accumulation of leukocytes in the spent dialysate 130 will result in increased turbidity or turbidity of the spent dialysate 130. As the turbidity increases, more white blood cells in the spent dialysate 130 scatter light emitted by the illumination element 206 into the spent dialysate 130. The scattered light sensor 208a will receive a stronger light signal and the transmitted light sensor 208b will receive a weaker light signal. Each light signal detected by the scattered light sensor 208a or the transmitted light sensor 208b may be used separately to correlate with the turbidity of the spent dialysate 130. Alternatively, the two optical signals may be used together to derive an optical ratio that may be correlated to turbidity. Combining the light signals from the scattered light sensor 208a and the transmitted light sensor 208b may increase the sensitivity of the light measurement compared to the light signal alone to better correlate with turbidity to detect infection. Combining the light signals also helps to improve reliability, especially in the event that the illumination element 206 deteriorates over time, such as a decrease in brightness.

In some embodiments, the device 200 further includes a set of lenses 210 that collimate the light emitted by the illumination element 206 into the fluid element 204 and/or focus the light on the optical sensor 208. The lens 210 helps to improve the signal-to-noise ratio(s) and sensitivity of the optical measurement. For example, as shown in fig. 2B, a lens 210 (which may include one or more condenser lenses) may be disposed in front of the illumination element 206 to collimate light emitted therefrom into a parallel beam that will help minimize light scattering before the light reaches the fluid element 204. Likewise, a lens 210 (e.g., a condenser lens) may be disposed in front of the scattered light sensor 208a and/or the transmitted light sensor 208b to focus light on the optical sensor 208, respectively. It is noted that the optical sensor 208 is located at the focal length of the lens 210, so that the light is effectively focused. The lens 210 may be disposed on a support base 212 attached to the chamber module 202, such as by using an optical adhesive that cures under ultraviolet light.

The fluid element 204 is a disposable component that is replaced each time the device 100 is used. The device 200 may be reused with the next disposable fluid element 204 for use in the next peritoneal dialysis treatment. The fluid element 204 may be pre-sterilized using a suitable method (e.g., gamma, ethylene oxide, or electron beam) prior to use in peritoneal dialysis treatment. The fluid element 204 may be pre-installed as part of a disposable line for use in the apparatus 100. The patient 102 needs to connect the device 200 to the fluid element 204 before beginning the peritoneal dialysis treatment.

In one embodiment as shown in fig. 3A, the fluid element 204 is part of the common line 106 or is connected to the common line 106, and the patient 102 connects the device 200 to the common line 106. In one embodiment, as shown in fig. 3B, the fluid element 204 is part of the drainage line 118 or is connected to the drainage line 118, and the patient 102 connects the device 200 to the drainage line 118.

The patient 102 may use the device 200 to measure the turbidity of the waste dialysate 130 of the patient 102, which waste dialysate 130 is discharged along the common line 106 and the drain line 118 to the drain bag 116. In an example, prior to initiating a peritoneal dialysis treatment, the patient 102 can use the device 200 to measure turbidity during an initial drainage phase. The initial drainage phase removes spent dialysate 130 from a previous abdominal session. In another example, during peritoneal dialysis treatment, the patient 102 can measure turbidity using the device 200 as the spent dialysate 130 flows along the common line 106 and the drain line 118 to the drain bag 116. In another example, the patient 102 can use the device 200 to measure turbidity during the final drainage phase at the end of a peritoneal dialysis treatment. The final drainage phase removes the last spent dialysate 130 from the abdomen before the patient 102 fills the abdomen with fresh dialysate from the fresh bag 110.

In addition, the apparatus 200 can measure turbidity in a dynamic state as the spent dialysate 130 flows through (e.g., at a flow rate of 100 ml/min) the fluid element 204. Thus, the measurement of turbidity can be integrated with the peritoneal dialysis treatment workflow, which would be less cumbersome for the patient 102 and reduce interruptions in treatment, rather than having to manually collect a sample of the waste dialysate 130 to make the measurement.

The device 200 may be calibrated before the patient 102 uses it to measure turbidity and detect infection. It has been found empirically that the optical ratio (y) between the scattered and transmitted light signals is linearly related to the turbidity value (x), where the linear equation is y=mx+c. Although the sensitivity of the device 200 may be represented by a gradient (m), the light intensity of the illumination element 206, the sensitivity of the optical sensor 208, and the baseline clarity of the transparent chamber module 202 may be slightly different, such that the baseline optical ratio may be different between different devices 200 in the absence of a turbid fluid.

Two exemplary devices 200 of the same design but different components, such as different housing modules 202, different illumination elements 206, different optical sensors 208, and different lenses 210, are used to determine a gradient (m) representing the sensitivity of the device 200. Using an initial liquid having a known turbidity value (measured in nephelometric turbidity units (Nephelometric Turbidity Units, NTU)), e.g. Baxter Peritoneal dialysis solution. The initial liquid passes through the fluidic element 204 and the device 200 measures the optical ratio of the initial liquid for different turbidity values. The optical ratios (y-axis) of the different peritoneal dialysis solutions to their respective NTUs (x-axis) are plotted as graphs 300, 310 for the two devices 200, as shown in fig. 4A and 4B. Gradient (m) was 0.2933 and 0.291, respectively, and offset values (c) were 4.5426 and 5.4636, respectively. The results show that two devices 200 of the same design but different components have a gradient (m) of about 0.29 sharing the same sensitivity or reaction slope. Thus, sensitivity is specific to the design of the device 200, even though different components may be used.

Since the results demonstrate that devices 200 having the same design have substantially the same gradient (m), a calibration procedure may be performed prior to use of the device 200, including determining an offset value (c) for the device 200. The calibration procedure is performed using the linear equation y=0.29x+c, and using a single initial liquid (e.g., fresh dialysis fluid in the fresh bag 110) with a known NTU.

The control module (which includes a computer processor) may be configured to perform a calibration procedure of a series of computerized steps. The steps include measuring an optical property of light that has interacted with fresh dialysate in the fluid element 204, correlating the optical property with a turbidity value of the fresh dialysate, and deriving an optical turbidity correlation curve (optical-turbidity profile) of the device 200 based on the correlation. The optical haze correlation curve is represented by the linear equation y=0.29x+c, where the offset value (c) is now known. Once calibrated, the device 200 can be used for peritoneal dialysis, and the optical turbidity correlation curve is configured to determine the turbidity of the waste dialysate 130 from the patient 102 based on the optical properties of light that has interacted with the waste dialysate 130 in the fluid element 204.

The optical turbidity correlation curve of the device 200 can be used to predict the turbidity value of the spent dialysate 130. As shown in graph 320 in fig. 4C, predicted turbidity value 322 is plotted against turbidity value 324 measured using a commercial turbidity meter. Commercial turbidimeters are large and expensive devices that measure static fluid turbidity, while the apparatus 200 differs in that it can measure fluid turbidity in a dynamic state (i.e., when fluid is flowing). As shown in graph 320, it has been found that the predicted turbidity value 322 and the measured turbidity value 324 are very close to each other. This illustrates that the calibration procedure can effectively calibrate the device 200 to derive an optical turbidity correlation curve for determining the turbidity of the spent dialysate 130.

As described above, the control module is configured to measure the turbidity of the spent dialysate 130 based on optical properties (e.g., optical ratio). If the dialysate turbidity of the patient 102 meets a set of predefined conditions with the historical dialysate turbidity, the dialysate turbidity is indicative of peritonitis. In an example, the predefined condition may include that the dialysate turbidity is higher than an average historical dialysate turbidity over a predefined period. More specifically, the predefined condition may include that the dialysate turbidity is higher than a predefined percentage (e.g., 10%) over the last several days (e.g., 3 to 5 days, one week, or more) than the average of the historical dialysate turbidity. In another example, the predefined condition may include the dialysate turbidity exceeding the average of the historical dialysate turbidity by a predefined number of standard deviations (e.g., 1, 2, or 3 standard deviations) over the past several days (e.g., 3 to 5 days, one week, or more). Upon determining that the dialysate turbidity meets the predefined condition, the device 200 can trigger an alarm or alert informing the patient 102 that he/she is primarily indicative of peritonitis.

The device 200 provides a more objective way to measure the turbidity of the spent dialysate 130 and enables earlier and/or more accurate detection of infection (e.g., peritonitis) of the patient 102. The device 200 may reduce the risk of false positives and missing a real peritonitis case compared to manual visual observation of the patient 102, where there is a problem with inconsistent quality of the examination. Furthermore, the apparatus 200 is small and can be easily integrated with the device 100, as compared to existing large and expensive commercial turbidimeters that measure static fluid turbidity.

On the other hand, turbidity is not a specific indicator of peritonitis, which may be attributed to other factors. For example, the turbid appearance of the spent dialysate 130 can be caused by non-pathogenic processes such as general immune response, spontaneous fibrin generation, and abdominal cavity air accumulation (pneumo). The high fat diet of patient 102 can also cause accumulation of lipoproteins and triglycerides, leading to visual diagnosis of opalescent dialysate and confounding peritonitis. Thus, the device 200 is suitable as an objective way of early stage screening Cha Fumo inflammation, followed by additional checks to confirm whether the patient 102 does have peritonitis.

Validation assays are typically performed using standard peritonitis test strips (e.g., leukostix reagent strips) that can specifically react to the presence of leukocyte esterases released primarily by neutrophils (a type of leukocyte). Peritonitis is typically associated with an increase in the number and percentage of neutrophils in the spent dialysate 130. Peritonitis is usually detected using clinical criteria of over 100 cells/μl and over 50% neutrophils. In addition, even if absolute leukocyte counts are less than 100 cells/μl, neutrophils in the spent dialysate 130 account for more than 50% of leukocytes and are a strong indicator of peritonitis. Typically, the patient 102 dips the reagent strip into the collected sample of spent dialysate 130. Once the reagent strip is wetted by the spent dialysate 130, the patient 102 must remove the reagent strip and wait for several minutes before determining a color change of the reagent strip. Any significant deviation from the protocol design, such as too long or too early or too late soaking of the strip to determine the color change, may result in erroneous determination of the test result.

In some representative and exemplary embodiments of the present invention, referring to fig. 5, there is an apparatus 400 for use with a peritoneal dialysis device 100 to monitor infection of a patient 102 for peritoneal dialysis. The apparatus 400 includes a housing module 402 that is detachably connected to a fluid element 404 configured to receive the spent dialysate 130 from the patient 102. The fluid element 404 may have various cross-sectional shapes, such as a cylindrical shape. The apparatus 400 optionally includes a set of illumination elements 406 disposed on the housing module 402 and configured to emit light into the fluid element 404. The apparatus 400 includes a color sensor 408, such as an RGB color sensor, disposed on the housing module 402. The color sensor 408 is configured to measure color information of a reagent test element 410 (e.g., a leukostix reagent strip) disposed in the fluid element 404, wherein the reagent test element 410 has reacted with the spent dialysate 130 in the fluid element 404, which results in a color change of the reagent test element 410. Reagent test element 410 may be illuminated by illumination element 406 (if present) and/or ambient illumination. The apparatus 400 includes a control module configured to monitor for infection (e.g., peritonitis) based on color information representative of enzyme activity in the spent dialysate 130, which is indicative of infection of the patient 102.

In some embodiments, the lighting element 406 includes one or more Light Emitting Diodes (LEDs). For example, the LEDs may include white LEDs. White light is generally preferred to accurately measure the color information of the reagent test element 410.

The fluid element 404 (which includes the reagent test element 410) is a disposable component that is replaced each time the device 100 is used. The device 400 may be reused with the next disposable fluid element 404 for use in the next peritoneal dialysis treatment. The fluid element 404 may be pre-sterilized using suitable methods prior to use in its peritoneal dialysis treatment. The fluid element 404 may be pre-installed as part of a disposable line for use in the apparatus 100. Prior to initiating the peritoneal dialysis treatment, the patient 102 needs to connect the device 400 to the fluid element 404. Prior to use of the device 400, the reagent test element 410 may be manually inserted into the fluid element 404 by the patient 102. Alternatively, the reagent test element 410 may be pre-inserted into the fluid element 404, for example, the fluid element 404 may be prepared in the form of the reagent test element 410 sealed inside thereof.

In one embodiment as shown in fig. 6A, the fluid element 404 is part of the common line 106 or is connected to the common line 106, and the patient 102 connects the device 400 to the common line 106. In one embodiment, as shown in fig. 6B, the fluid element 404 is part of the drain line 118 or is connected to the drain line 118, and the patient 102 connects the device 400 to the drain line 118.

The patient 102 may use the device 400 to measure color information of the reagent test element 410 that has reacted with the waste dialysate 130 discharged by the patient 102 along the common line 106 and the drain line 118 to the drain bag 116. In an example, prior to beginning a peritoneal dialysis treatment, the patient 102 can use the device 400 to measure color information during an initial drainage phase. In another example, the patient 102 can use the device 400 to measure color information during peritoneal dialysis treatment as the spent dialysate 130 flows along the common line 106 and the drain line 118 to the drain bag 116. In another example, the patient 102 can use the device 400 to measure turbidity during the final drainage phase at the end of a peritoneal dialysis treatment.

Further, to control the wetting time of the reagent test element 410, the fluid element 404 may include a flow control mechanism configured to selectively communicate the spent dialysate 130 into and out of the fluid element 404. The device 400 may be connected to the common line 106 or the drain line 118. The fluid element 404 cooperates with the common line 106/drain line 118 to selectively control the flow of the spent dialysate 130 from the common line 106/drain line 118 into the fluid element 404 and out of the spent dialysate 130 from the fluid element 404 after a predefined duration. The predefined duration defines a wetting time of the reagent test element 410, such as in the range of 0.5 to 2 seconds, and ensures that the reagent test element 410 is properly wetted.

In one embodiment, as shown in FIG. 6A, the apparatus 400 is connected to the common line 106. Valve 420 connects common line 106 to fluid element 404 to control the flow of spent dialysate 130. The device 400 is hermetically sealed so that when the patient valve 105 is closed and the valve 420 is open, the direction of fluid flow is reversed, resulting in an increase in pressure within the device 400. This pressure compresses the air inside the device 400 and causes the dialysate level to rise, thus wetting the reagent test element 410. Subsequently, valve 420 is closed to ensure proper wetting of reagent test element 410 after a predefined duration. Thereafter, the patient valve 105 remains closed, the flow is reversed, and the valve 420 is opened, thereby releasing the pressure in the device 400 through the common line 106 and withdrawing the spent dialysate 130 from the device 400.

In one embodiment, as shown in fig. 6B, the device 400 is connected to the drain line 118. Valve 430 connects drain line 118 to fluid element 404 to control the flow of spent dialysate 130. The device 400 is hermetically sealed so that when the discharge valve 120 is closed, the valve 430 is opened and the pressure within the device 400 increases. This pressure compresses the air inside the device 400 and causes the dialysate level to rise, thus wetting the reagent test element 410. Subsequently, valve 430 is closed to ensure proper wetting of reagent test element 410 after a predefined duration. Thereafter, the drain valve 120 opens after the valve 430, thereby releasing the pressure in the device 400 through the drain line 120 and withdrawing the spent dialysate 130 from the device 400.

The control module (which includes a computer processor) is configured to perform a computerized method to monitor infection (e.g., peritonitis) based on the color information of the reagent test element 410. The method comprises the step of controlling the color sensor 408 to measure color information of the reagent test element 410 that has reacted with the spent dialysate 130 within a predefined duration. The method comprises the step of measuring color information of the reagent test element 410 for a predefined period of time after a predefined duration. The predefined time period (which may be in the range of 0.5 to 5 minutes after the predefined duration) ensures that the reagent test element 410 is measured within the correct time window. The method includes the steps of extracting RGB color data from the color information, monitoring the patient 102 for infection based on the RGB color data, wherein the RGB color data is representative of enzyme activity, which is indicative of the patient 102 for infection.

In some embodiments, the method includes the step of converting the extracted RGB color data into second color data in a second color space and determining the enzymatic activity based on the second color data, wherein the second color data is representative of the enzymatic activity. The second color space may include CIELAB, CIE XYZ, or YCbCr color space.

In a specific embodiment, the RGB color data is converted to a CIELAB color space. The CIELAB color space (also known as the L x a x b x color space) is defined by the international commission on illumination (International Commission on Illumination, CIE) and represents colors as three values-L x representing light intensity (black to white), a x representing colors from green to red, and b x representing colors from blue to yellow. The values a and b represent four distinct colors of human vision-red, green, blue and yellow. Thus, the CIELAB color space is more closely related to the human eye's visual perception characteristics.

The method may include denoising the RGB color data, followed by converting the denoised RGB color data into a CIELAB color space. For example, the RGB color data may be de-noised using methods such as filtering and/or outlier removal. For example, outlier removal may include removing RGB color data that is outside of the third quarter-bit range. The method may include deriving an index parameter from the CIELAB color data of the de-noised RGB color data conversion, and determining the enzyme activity based on the index parameter. More specifically, RGB color data over a predefined period of time is converted into a plurality of samples of CIELAB color data. For each sample, the average of the a values is removed and the absolute value of a (where the average is removed) is calculated. The absolute values of a x for the samples for the predefined period are summed and then normalized by the number of samples. Deriving an index parameter from the normalized absolute value of a.

As shown in the graph 500 of fig. 7, the index parameter is correlated with the enzyme activity. The enzymatic activity may be related to the degree of leukocyte esterase activity in the dialysate. Leukocyte esterase activity correlates with neutrophil count and acts as a surrogate marker indicating the presence of neutrophil count in the dialysate. Thus, the enzymatic activity in the spent dialysate 130 can be determined based on the determined index parameters and the graph 500, wherein the enzymatic activity can be indicative of peritonitis.

The advantage of using the CIELAB color space is that it is almost independent of color intensity (due to the light intensity from the lighting elements 406) and is more dependent on color differences. The graph 500 shows that different degrees of leukocyte esterase activity can be effectively distinguished based on the index parameters. Distinguishing leukocyte esterase activity by index parameters has a higher resolution and reduces subjectivity of the measurement than conventional approaches using some palettes as references (patient 102 may have difficulty distinguishing these colors). A threshold can be empirically developed from clinical data to diagnose positive and negative cases of peritonitis. The threshold for positive case diagnosis can be fine-tuned to strike a balance between sensitivity and specificity of peritonitis detection.

In a specific embodiment, the RGB color data is converted to CIE XYZ color space. In the CIE XYZ color space, X represents a mixture of non-negative RGB colors, Y represents luminance, and Z represents blue channel information (blue channel information). Similar to the index parameters from the CIELAB color data, the corresponding index parameters can be derived from the second color data in the CIE XYZ color space with minimal dependence on luminance and removal of blue channel information.

In a specific embodiment, the RGB color data is converted into YCbCr color space. In the YCbCr color space, Y represents a luminance or light intensity component, cb represents a blue-difference chrominance (blue-difference chroma) component, and Cr represents a red-difference chrominance (red-difference chroma) component. Similar to the index parameters from the CIELAB color data, the corresponding index parameters may be derived from the second color data in the YCbCr color space, where the Cr component in the YCbCr color space may be used to replace the a-value in the CIELAB color space.

In one embodiment, the RGB color data may be used directly to derive corresponding index parameters to determine enzyme activity.

In some embodiments, the apparatus 200, 400 is used in combination in the device 100 to increase the overall specificity of infection diagnostic accuracy. The device 200 can perform early screening of infection based on the turbidity of the spent dialysate 130, and if the early screening is preliminary to an infection, the trigger device 400 performs more sensitive infection detection. The devices 200, 400 may be used sequentially such that when turbidity initially indicates an infection, the patient 102 then inserts the reagent test element 410 into the fluid element 404 for a confirmatory check. Alternatively, the patient 102 may use the fluid element 404 already containing the reagent test element 410. This saves the number of reagent test elements 410 used during peritoneal dialysis, as the device 400 is only used when the device 200 triggers an early screening alarm.

In one embodiment, as shown in fig. 8A, the patient 102 connects the devices 200, 400 to the common line 106. In one embodiment, as shown in fig. 8B, the patient 102 connects the devices 200, 400 to the drain line 118. The patient 102 may use the apparatus 200, 400 during an initial drainage phase prior to beginning a peritoneal dialysis treatment, during a peritoneal dialysis treatment, or during a final drainage phase at the end of a peritoneal dialysis treatment.

In some representative and exemplary embodiments of the present invention, referring to fig. 9, there is an apparatus 600 for use with a peritoneal dialysis device 100 to monitor infection of a patient 102 for peritoneal dialysis. The device 600 is an integrated device that combines the functions of the devices 200, 400. The apparatus 600 includes a housing module 602 that is detachably connected to a fluid element 604 configured to receive the spent dialysate 130 from the patient 102. The fluidic element 604 may have various cross-sectional shapes, such as a cylinder. The apparatus 600 includes a set of illumination elements 606 disposed on the chamber module 602 and configured to emit light into the fluid element 604.

The device 600 includes a set of optical sensors 608 disposed on the housing module 602 and configured to measure optical properties of light that has interacted with the spent dialysate 130 in the fluid element 204 and to measure color information of a reagent test element 610 disposed in the fluid element 604, wherein the reagent test element 610 has reacted with the spent dialysate 130 in the fluid element 604, which results in a color change of the reagent test element 610. The apparatus 600 includes a control module configured to measure the turbidity of the spent dialysate 130 based on optical properties, wherein the dialysate turbidity indicates the patient 102 is infected if the dialysate turbidity and the historical dialysate turbidity of the patient 102 meet a set of predefined conditions. The control module is further configured to monitor for an infection based on color information representative of enzyme activity in the spent dialysate 130, which is indicative of the infection.

The optical sensor 608 includes a scattered light sensor 608a that measures light that has been scattered by the spent dialysate 130, and a transmitted light sensor 608b that measures light that has been transmitted through the spent dialysate 130. The optical sensor 608 further includes a color sensor 608c that measures color information of the reagent test element 610. It should be appreciated that the scattered light sensor 608a, the transmitted light sensor 608b, and the color sensor 608c are similar to the scattered light sensor 208a, the transmitted light sensor 208b, and the color sensor 408, respectively.

The illumination element 606 includes at least a first illumination element 606a that cooperates with the scattered light sensor 608a and the transmitted light sensor 608b. The illumination element 606 includes at least one second illumination element 606b that cooperates with the color sensor 608c. It should be appreciated that the first and second illumination elements 606a and 606b are similar to illumination elements 206 and 406, respectively. Alternatively, the illumination element 606 may comprise a single illumination element that mates with all of the optical sensors 608.

The fluid element 604 may include a flow control mechanism configured to selectively control communication of the waste dialysate 130 into and out of the waste dialysate 130 from the fluid element 604 after a predefined duration. Similar to the fluidic element 404, the predefined duration defines a wetting time of the reagent test element 610, such as in the range of 0.5 to 2 seconds. When the spent dialysate 130 is in communication in the fluid component 604, the scattered light sensor 608a and the transmitted light sensor 608b can measure the turbidity of the spent dialysate 130. Once the spent dialysate 130 has been drained from the fluid component 604, the color sensor 608c continues to measure color information of the reagent test component 610 that has reacted with the spent dialysate 130.

The fluidic element 604 (which includes the reagent test element 610) is a disposable component that is replaced each time the device 100 is used. The device 600 may be reused with the next disposable fluid element 604 for use in the next peritoneal dialysis treatment. The fluid element 604 may be pre-sterilized using a suitable method prior to use in peritoneal dialysis treatment. The fluid element 604 may be pre-installed as part of a disposable line for the device 100. Prior to initiating the peritoneal dialysis treatment, the patient 102 needs to connect the device 600 to the fluid element 604 and optionally calibrate the device 600. The reagent test element 610 may be manually inserted into the fluid element 604 by the patient 102 prior to use of the device 600. Alternatively, the reagent test element 610 may be pre-inserted into the fluid element 604, for example, the fluid element 604 may be prepared in the form of a reagent test element 610 sealed within.

The patient 102 first uses the device 600 to measure color information of the reagent test element 610 that has reacted with the spent dialysate 130 during an initial drainage phase that removes the spent dialysate 130 from a previous abdominal phase. The flow control mechanism controls the inflow and outflow of the spent dialysate 130 in the fluid element 604 for a predefined duration. Subsequently, the patient 102 initiates a peritoneal dialysis treatment and uses the device 600 to measure the turbidity of the spent dialysate 130 discharged by the patient 102, wherein the spent dialysate 130 continues to flow in the fluid element 604. In an example, as the spent dialysate 130 flows along the common line 106 and the drain line 118 to the drain bag 116, the patient 102 can use the device 600 to measure turbidity during peritoneal dialysis treatment. In another example, the patient 102 can use the device 600 to measure turbidity during the final drainage phase at the end of a peritoneal dialysis treatment. The measurement results based on the turbidity of the spent dialysate 130 and the color information of the reagent test element 610 can be complementary to each other and can improve the overall accuracy of infection detection. The device 600 can detect infection, such as peritonitis, with greater sensitivity and specificity.

In one embodiment as shown in fig. 10A, the fluid element 604 is part of the common line 106 or is connected to the common line 106, and the patient 102 connects the device 600 to the common line 106. The valve 620 may connect the common line 106 to the fluidic element 604 to control the flow of the spent dialysate 130. In one embodiment, as shown in fig. 10B, the fluid element 604 is part of the drainage line 118 or is connected to the drainage line 118, and the patient 102 connects the device 600 to the drainage line 118. Valve 630 may connect drain line 118 to fluid element 604 to control the flow of spent dialysate 130. It should be appreciated that the operation of the valves 620, 630 is similar to the valves 420, 430 described above.

Fig. 11A and 11B illustrate some other configurations of the device 600. Specifically, the cabinet module 602 may be a polygonal structure having a plurality of sides. In a particular embodiment as shown in fig. 11A, a first illumination element 606a cooperating with a scattered light sensor 608a and a transmitted light sensor 608b is provided on one side and the transmitted light sensor 608b is provided on the opposite side. The scattered light sensor 608a is arranged on the other side such that it is perpendicular to the first illumination element 606a and the transmissive light sensor 608b. The color sensor 608c and the second illumination element 606b cooperating with the color sensor 608c are arranged on two other different sides. In one embodiment, as shown in FIG. 11B, there is a single illumination element 606 that mates with all of the optical sensors 608. The illumination element 606 and the transmissive light sensor 608b are disposed on opposite sides of each other. The scattered light sensor 608a is arranged on the other side such that it is perpendicular to the illumination element 606 and the transmitted light sensor 608b. The color sensor 608c is disposed on the other side.

It should be appreciated that the various aspects of the devices 200, 400, 600 may be equally applicable to each other and are not described in detail for brevity purposes. It should also be appreciated that the control modules described herein include a processor, memory, and various other modules or components. The modules and their components are configured to perform various operations or steps and are configured as part of a processor. Such operations or steps are performed in response to non-transitory instructions operated on or executed by a processor. The memory is used to store instructions and data that may be read during program execution. In some contexts, memory may refer to computer-readable storage media and/or non-transitory computer-readable media. Non-transitory computer readable media include all computer readable media, with the sole exception of the transitory transmitted signal itself.

Thus, the apparatus 200, 400, 600 provides an improved method of more accurately monitoring infection (e.g., peritonitis) of a peritoneal dialysis patient 102. For example, the apparatus 200, 400 allows for early screening of the preliminary signs of Cha Fumo inflammation, which can then be confirmed by a reagent test. Screening and then confirmation is of significant economic benefit, as screening is very inexpensive and patient 102 incurs little if any expense for every day use.

Patients 102 with or at risk of having peritonitis may be identified earlier, so that medical intervention may be provided earlier. Once peritonitis is diagnosed, a treatment period of about 4 to 10 days is typically required. The earlier the diagnosis, the less damage the peritonitis has to the peritoneum, and the more effective and less costly the medical treatment can be. Peritonitis is associated with a high risk of cardiovascular disease, and severe infections may lead to systemic sepsis and even death. Thus, early treatment means that the infected patient 102 can be treated more effectively and mortality can be reduced. The device 200, 400, 600 can monitor peritonitis earlier and more accurately, and more patients 102 can employ the device 200, 400, 600 when performing home dialysis.

In the foregoing detailed description, specific embodiments of the invention related to an apparatus for monitoring peritoneal dialysis infection are described with reference to the drawings provided. The description of the various embodiments herein is not intended to claim or be limited to the particular or particular forms of the invention, but is to be construed as merely illustrative of non-limiting examples of the invention. The present invention is directed to solving at least one of the above-mentioned problems associated with the prior art. Although only a few specific embodiments of the invention have been disclosed herein, those skilled in the art will appreciate that, in light of the present disclosure, various changes and/or modifications can be made to the specific embodiments disclosed without departing from the scope of the invention. The scope of the invention and the claims are therefore not limited to the specific embodiments described herein.

Claims

1. An apparatus for monitoring infection in a peritoneal dialysis patient, comprising:

a set of lighting elements disposed on the chamber module and configured to emit light into the fluid element;

a set of optical sensors disposed on the housing module and configured to measure optical properties of light after interaction with spent dialysate in the fluidic element; and

a control module configured to measure turbidity of the spent dialysate based on the optical property,

wherein the dialysate turbidity is indicative of a patient infection if the dialysate turbidity meets a set of predefined conditions with the patient's historical dialysate turbidity.

2. The device according to claim 1, wherein the optical sensor comprises a scattered light sensor for measuring light that has been scattered by the waste dialysate and/or a transmitted light sensor for measuring light that has been transmitted through the waste dialysate.

3. The apparatus of claim 2, wherein the optical property comprises an optical ratio between the scattered light and the transmitted light.

4. A device as claimed in any one of claims 1 to 3, further comprising a set of lenses for collimating light emitted by the illumination element into the fluid element and/or focusing the light on the optical sensor.

5. The apparatus of any one of claims 1 to 4, further comprising the fluid element removably connected to the tank module.

6. The apparatus of any one of claims 1 to 5, wherein the predefined condition comprises the dialysate turbidity being higher than an average historical dialysate turbidity over a predefined period.

7. An apparatus for monitoring infection in a peritoneal dialysis patient, comprising:

a control module configured to monitor for infection based on the color information, the color information representing an enzymatic activity in the spent dialysate, indicative of patient infection.

8. The apparatus of claim 7, further comprising a set of lighting elements disposed on the chamber module, the lighting elements configured to emit light into the fluid element.

9. The apparatus of claim 7 or 8, further comprising the fluid element removably connected to the tank module.

10. The apparatus of claim 9, wherein the fluid element comprises a flow control mechanism configured to selectively communicate the spent dialysate into and out of the fluid element.

11. The apparatus of claim 10, wherein the flow control mechanism is configured to selectively control the flow of the spent dialysate into the fluid element and out of the fluid element after a predefined duration.

12. The apparatus of any of claims 7 to 11, wherein the color sensor comprises an RGB color sensor and the control module is configured to:

extracting RGB color data from the color information;

converting the RGB color data into second color data in a second color space; and

The enzyme activity is determined based on the second color data.

13. The apparatus of claim 12, wherein the control module is configured to denoise the RGB color data and convert the denoised RGB color data to the second color data.

14. The apparatus of claim 12 or 13, wherein the control module is configured to derive an indicator parameter from the second color data, wherein the enzyme activity is determined based on the indicator parameter.

15. The apparatus of any one of claims 12 to 14, wherein the second color space comprises a CIELAB, CIE XYZ, or YCbCr color space.

16. An apparatus for monitoring infection in a peritoneal dialysis patient, comprising:

a set of optical sensors disposed on the housing module and configured to:

measuring an optical property of light that has interacted with the spent dialysate in the fluid element; and

a control module configured to:

measuring a turbidity of the spent dialysate based on the optical property, the dialysate turbidity being indicative of a patient infection if the dialysate turbidity meets a set of predefined conditions with a patient's historical dialysate turbidity; and

17. The apparatus of claim 16, wherein the optical sensor comprises:

a scattered light sensor for measuring light that has been scattered by the spent dialysate;

a transmission light sensor for measuring light that has been transmitted through the spent dialysate; and

a color sensor for measuring the color information.

18. The apparatus of claim 17, wherein the optical property comprises an optical ratio between the scattered light and the transmitted light.

19. The apparatus of any one of claims 16 to 18, further comprising the fluid element removably connected to the tank module.

20. The apparatus of claim 19, wherein the fluid element comprises a flow control mechanism configured to selectively communicate the spent dialysate into and out of the fluid element.

21. The apparatus of claim 20, wherein the flow control mechanism is configured to selectively control the flow of the spent dialysate into the fluid element and out of the spent dialysate from the fluid element after a predefined duration.

22. The apparatus of any one of claims 16 to 21, wherein the optical sensor comprises an RGB color sensor that measures the color information and the control module is configured to:

extracting RGB color data from the color information;

the enzyme activity is determined based on the second color data.

23. The apparatus of claim 22, wherein the control module is configured to denoise the RGB color data and convert the denoised RGB color data to the second color data.

24. The apparatus of claim 22 or 23, wherein the control module is configured to derive an indicator parameter from the second color data, wherein the enzyme activity is determined based on the indicator parameter.

25. The apparatus of any one of claims 22 to 24, wherein the second color space comprises a CIELAB, CIE XYZ, or YCbCr color space.

26. A computerized method of monitoring infection in a peritoneal dialysis patient, comprising:

measuring color information of a reagent test element that has reacted with waste dialysate from a patient;

extracting RGB color data from the color information; and

infection is monitored based on the RGB color data, which represents enzyme activity in the spent dialysate, which is indicative of patient infection.

27. The method of claim 26, further comprising converting the RGB color data to second color data in a second color space and monitoring for infection based on the second color data.

28. The method of claim 27, further comprising denoising the RGB color data and converting the denoised RGB color data into the second color data.

29. The method of claim 27 or 28, further comprising deriving an index parameter from the second color data and determining the enzyme activity based on the index parameter.

30. The method of any one of claims 26 to 29, wherein the second color space comprises a CIELAB, CIE XYZ, or YCbCr color space.